A newly designed thread-like robot can deliver clot reducing therapies in response to stroke or other brain blockages

0
1022

MIT engineers have developed a magnetically steerable, thread-like robot that can actively glide through narrow, winding pathways, such as the labrynthine vasculature of the brain.

In the future, this robotic thread may be paired with existing endovascular technologies, enabling doctors to remotely guide the robot through a patient’s brain vessels to quickly treat blockages and lesions, such as those that occur in aneurysms and stroke.

Stroke is the number five cause of death and a leading cause of disability in the United States.

If acute stroke can be treated within the first 90 minutes or so, patients’ survival rates could increase significantly,” says Xuanhe Zhao, associate professor of mechanical engineering and of civil and environmental engineering at MIT.

“If we could design a device to reverse blood vessel blockage within this ‘golden hour,’ we could potentially avoid permanent brain damage. That’s our hope.”

Zhao and his team, including lead author Yoonho Kim, a graduate student in MIT’s Department of Mechanical Engineering, describe their soft robotic design in the journal Science Robotics.

The paper’s other co-authors are MIT graduate student German Alberto Parada and visiting student Shengduo Liu.

In a tight spot

To clear blood clots in the brain, doctors often perform an endovascular procedure, a minimally invasive surgery in which a surgeon inserts a thin wire through a patient’s main artery, usually in the leg or groin. Guided by a fluoroscope that simultaneously images the blood vessels using X-rays, the surgeon then manually rotates the wire up into the damaged brain vessel.

A catheter can then be threaded up along the wire to deliver drugs or clot-retrieval devices to the affected region.

Kim says the procedure can be physically taxing, requiring surgeons, who must be specifically trained in the task, to endure repeated radiation exposure from fluoroscopy.

“It’s a demanding skill, and there are simply not enough surgeons for the patients, especially in suburban or rural areas,” Kim says.

The medical guidewires used in such procedures are passive, meaning they must be manipulated manually, and are typically made from a core of metallic alloys, coated in polymer, a material that Kim says could potentially generate friction and damage vessel linings if the wire were to get temporarily stuck in a particularly tight space.

The team realized that developments in their lab could help improve such endovascular procedures, both in the design of the guidewire and in reducing doctors’ exposure to any associated radiation.

Threading a needle

Over the past few years, the team has built up expertise in both hydrogels — biocompatible materials made mostly of water — and 3-D-printed magnetically-actuated materials that can be designed to crawl, jump, and even catch a ball, simply by following the direction of a magnet.

In this new paper, the researchers combined their work in hydrogels and in magnetic actuation, to produce a magnetically steerable, hydrogel-coated robotic thread, or guidewire, which they were able to make thin enough to magnetically guide through a life-size silicone replica of the brain’s blood vessels.

The core of the robotic thread is made from nickel-titanium alloy, or “nitinol,” a material that is both bendy and springy.

Unlike a clothes hanger, which would retain its shape when bent, a nitinol wire would return to its original shape, giving it more flexibility in winding through tight, tortuous vessels.

The team coated the wire’s core in a rubbery paste, or ink, which they embedded throughout with magnetic particles.

Finally, they used a chemical process they developed previously, to coat and bond the magnetic covering with hydrogel — a material that does not affect the responsiveness of the underlying magnetic particles and yet provides the wire with a smooth, friction-free, biocompatible surface.

They demonstrated the robotic thread’s precision and activation by using a large magnet, much like the strings of a marionette, to steer the thread through an obstacle course of small rings, reminiscent of a thread working its way through the eye of a needle.

This shows the thread robot

MIT engineers develop magnetically steerable robotic thread (in black), small enough to work through narrow spaces, such as the vasculature of the human brain. Researchers envision the technology may be used in the future to clear blockages in patients with stroke and aneurysms. The image is credited to the researchers/MIT.

The researchers also tested the thread in a life-size silicone replica of the brain’s major blood vessels, including clots and aneurysms, modeled after the CT scans of an actual patient’s brain.

The team filled the silicone vessels with a liquid simulating the viscosity of blood, then manually manipulated a large magnet around the model to steer the robot through the vessels’ winding, narrow paths.

Kim says the robotic thread can be functionalized, meaning that features can be added — for example, to deliver clot-reducing drugs or break up blockages with laser light.

To demonstrate the latter, the team replaced the thread’s nitinol core with an optical fiber and found that they could magnetically steer the robot and activate the laser once the robot reached a target region.

When the researchers ran comparisons between the robotic thread coated versus uncoated with hydrogel, they found that the hydrogel gave the thread a much-needed, slippery advantage, allowing it to glide through tighter spaces without getting stuck. In an endovascular surgery, this property would be key to preventing friction and injury to vessel linings as the thread works its way through.

And just how can this new robotic thread keep surgeons radiation-free? Kim says that a magnetically steerable guidewire does away with the necessity for surgeons to physically push a wire through a patient’s blood vessels. This means that doctors also wouldn’t have to be in close proximity to a patient, and more importantly, the radiation-generating fluoroscope.

Credit: MIT

In the near future, he envisions endovascular surgeries that incorporate existing magnetic technologies, such as pairs of large magnets, the directions of which doctors can manipulate from just outside the operating room, away from the fluoroscope imaging the patient’s brain, or even in an entirely different location.

“Existing platforms could apply magnetic field and do the fluoroscopy procedure at the same time to the patient, and the doctor could be in the other room, or even in a different city, controlling the magnetic field with a joystick,” Kim says. “Our hope is to leverage existing technologies to test our robotic thread in vivo in the next step.”

Funding: This research was funded, in part, by the Office of Naval Research, the MIT Institute for Soldier Nanotechnologies, and the National Science Foundation (NSF).


A stroke is an acute compromise of the cerebral perfusion or vasculature or cerebrovascular accident (CVA).  Approximately 85% strokes are ischemic and rest are hemorrhagic. [1] In this discussion we mainly confine to ischemic strokes. Over the past several decades, the incidence of stroke and mortality are decreasing. [2] 

Stroke is the leading cause of adult disability worldwide.  It is thus critical to recognize stroke early and treat it rapidly to prevent or minimize morbidity and mortality. There are many causes of stroke.

Hypertension is the leading cause of ischemic stroke.  In the younger population, there are numerous causes of stroke including clotting disorders, carotid dissection, and illicit drug abuse. In the acute setting, a quick history and examination to be performed. As time is brain it is very important not to waste any time.

As acute stroke management is evolving rapidly one must consider patients for IV tPA up to 4.5 hours and mechanical thrombectomy up to 6 hours. Recent DAWN trial showed that one can extend the window for mechanical thrombectomy up to 24 hours in selected cases of large vessel occlusion. [3]

Etiology

Ischemic etiologies can further be divided into embolic, thrombotic, and lacunar. In general, the common risk factors for stroke include hypertension, diabetes, smoking, obesity, atrial fibrillation, and drug use.

Of all the risk factors, Hypertension is the most common modifiable risk factor for stroke. Hypertension is most prevalent in blacks and also occur earlier in life. [1] According to JNC8, the recommended blood pressure targets in patients with stroke should be less than 140/90mm Hg. [4] 

Chronic uncontrolled hypertension causes small vessel strokes mainly in the internal capsule, thalamus, pons, and cerebellum.[5]Lifestyle measures such as weight loss, salt restriction, taking more fruits and vegetables (Such as Mediterranean diet)[6] are helpful in decreasing the blood pressure. Every 10 mm Hg reduction in blood pressure is associated with a 1/3rd reduction in stroke risk in primary prevention. [7] 

One-third of the adults in the USA have elevated LDL, leading to plaque formation in the intracerebral vasculature. Eventually, due to the excessive plaque build-up thrombotic strokes occur. In the older population, the risk of cardioembolic stroke increases mainly due to atrial fibrillation.[8] The rest 20% of strokes are due to hemorrhagic in nature. Hemorrhagic etiologies can be from hypertension, aneurysm rupture, arteriovenous malformations, venous angiomas, bleeding due to illicit drugs like cocaine, hemorrhagic metastasis, amyloid angiopathy, and other obscure etiologies.

Lacunar strokes makeup about 20% of all ischemic strokes and result from occlusion of the small penetrating branches of the middle cerebral artery, vertebral or basilar artery or the lenticulostriate vessels. Typical causes of lacunar strokes include microemboli, fibrinoid necrosis secondary to vasculitis or hypertension, amyloid angiopathy, and hyaline arteriosclerosis.

Epidemiology

Stroke is the fifth leading cause of death in the US. The incidence of stroke is around 800,000 people annually. Stroke is the leading cause of disability. [9] The incidence of stroke has declined, but the morbidity has increased. Due to longer life expectancy, the lifetime risk of stroke is higher in women. Globally, at least 5 million people die from strokes and millions other remain disabled.

Pathophysiology

Stroke is the result of ischemia to an area of the brain. The Na+/K+ ATPase pumps fail mainly because of poor production of ATP and failure of the aerobic mechanism. Ischemia leads to depolarization of cells which results in calcium influx into cells, elevated lactic acid, acidosis, and free radicals. Cell death increases glutamate and leads to a cascade of chemicals (excitotoxicity). [10]

History and Physical

The most important piece of historical information that the clinician should obtain is the time of symptoms onset or time last seen normal.  This is critical because it determines the eligibility to receive rtPA or endovascular intervention for stroke. [11] Other important information to obtain is risk factors for arteriosclerosis and cardiovascular disease, diabetes, smoking, atrial fibrillations drug abuse, migraine, seizures, infection trauma or pregnancy.  

The stroke exam is a multi-person coordinated rapid exam.  While staff obtain vitals, attach telemetry, and obtain IV access, the physician performs a rapid neurological evaluation.  National Institutes of Health Stroke Scale (NIHSS) is routinely used to get the baseline evaluation. The exam has to be rapid as “time is brain.”  One must examine the following items:

  • The level of consciousness (alert and responsive, arouses to noxious stimuli, comatose…)
  • Language (fluency, naming, comprehension, repetition) 
  • Dysarthria (slurring) which may be picked up in the history
  • Motor (subtle arm weakness can be picked up by performing a pronator drift)
  • Visual field deficits
  • Eye movement abnormalities (in general if a gaze preference is present, the eyes deviate towards the side of the lesion)
  • Facial paralysis (asking the patient to smile)
  • Ataxia (finger to nose)

With a good history and physical exam, we can localize the stroke. There are various stroke syndromes.

Anterior Cerebral Artery (ACA) Infarction

There is significant collateral blood supply in the anterior circulating artery territory. So, pure ACA strokes are rare. The ACA distribution involves mainly Broca’s area, primary motor, primary sensory and pre-frontal cortex. So patients present with motor aphasia, personality issues, and contralateral leg weakness and numbness. Hand and face are usually spared.

Middle Cerebral Artery (MCA) Infarction

The middle cerebral artery has the main trunk (M1) and it divides into two M2 Branches. The M1 (horizontal branch) supplies the basal ganglia and M2 (Sylvian branches) supplies part of the parietal, frontal and temporal lobes. As MCA supplies a wide territory it is extremely important to rule out MCA occlusion. The MCA syndrome causes contralateral arm and facial numbness and weakness, gaze deviation towards the affected side. Aphasia in the left-sided lesions and neglect in the right-sided lesions.

Posterior Cerebral Artery (PCA) Infarction

The posterior cerebral artery mainly supplies occipital lobe, thalamus and some portion of the temporal lobe. The classic presentation of posterior cerebral artery stroke is homonymous hemianopsia. Apart from this hypersomnolence, cognitive issues, the hemisensory loss can be seen when the deep PCA is involved. Some times there is bilateral infarction of distal PCAs producing cortical blindness and the patient is unaware of the blindness and deny it. This is called Anton-Babinski syndrome.

Cerebellar Infarction

The patients with cerebellar strokes present with ataxia, dysarthria, nausea, vomiting, and vertigo. 

Lacunar strokes are due to occlusion of small perforating vessels and can be pure motor, pure sensory and ataxic hemiparetic strokes. In general, these strokes don’t impair memory, cognition, level of consciousness or speech.

The stroke can be quantified by the NIHSS scale which includes the following:

  • Visual function
  • Level of consciousness
  • Sensation and neglect
  • Motor function
  • Cerebellar function
  • Language

A high score suggests proximal vessel occlusion.

Evaluation

The initial workup of a stroke patient involves stabilizing the Airway, Breathing, and Circulation (ABC). This is followed by a rapid, concise, history and exam such as the NIHSS which is administered simultaneously as the patient gets IV access, telemetry, and labs were drawn.  The patient should then get a stat non-contrasted head CT or a combination of Head CT, CT Angiography, and perfusion imaging. “Time is brain,” and so we should not waste any time at all.  Ideally, rtPA should be prepared as imaging is occurring, and as soon as the non-contrasted head CT can be visualized, and a bleed is excluded, rtPA should be administered after discussing the risks and benefits, and excluding rtPA contraindications.  Time is critical, as only patients who get all the required studies within 4.5 hours qualify for potentially lifesaving thrombolysis.  After IV rtPA, the CT angiography should be reviewed to determine if the patient qualifies for endovascular therapy as well.

In recent years there are significant advancements in acute stroke care. Multiple stroke trials in 2015 showed that Endovascular thrombectomy in the first six hours is much better than standard medical care in patients with large vessel occlusion in the arteries of the proximal anterior circulation. These benefits sustained irrespective of geographical location and patient characteristics.[12]

Again in 2018, a significant paradigm shift happened in stroke care. DAWN trial showed significant benefits of Endovascular thrombectomy in patients with large vessel occlusion in the arteries of the proximal anterior circulation. This trial extended stroke window up to 24 hours in selected patients using perfusion imaging. Due to this, we can treat more patients even up to 24 hours. [3]

All patients should be treated with an antiplatelet agent and a statin, and be admitted for full stroke evaluation.  Hypertension is often seen in acute stroke.  This should not be aggressively treated. A baseline electrocardiogram is recommended. The following labs would be indicated when a diagnosis of stroke is entertained: 

  1. Basic metabolic panel (BMP)
  2. Complete blood count (CBC)
  3. Cardiac markers
  4. Coagulation profile: prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (PTT)Lipid Panel
  5. Hemoglobin A1C

A transthoracic echocardiogram, telemetry monitoring, and neck vessel imaging are necessary to elucidate the etiology of stroke.

Treatment / Management

Acute ischemic stroke patients who meet the criteria for rtPA and do not have any contraindications should receive IV rtPA. Patients who have large vessel occlusions should be evaluated for possible endovascular intervention. All patients suspected of having acute ischemic stroke should be admitted for a full neurological workup.  Neurology consultation should be obtained. The workup of acute ischemic stroke includes a search for a source of thrombus, which includes carotid artery evaluation by ultrasound, CTA, MRA, or conventional angiography.  A Transthoracic echocardiogram is obtained to ascertain for low ejection fraction, the cardiac source of the clot, or patent foramen ovale.  EKG and telemetry are obtained to ascertain for rhythms predisposing to stroke such as atrial fibrillation.  Labs such as a fasting lipid panel, and hemoglobin A1C, are obtained to ascertain for modifiable risk factors for stroke.  Other labs such as a hypercoagulable panel in young patients or B12 and syphilis testing in selected patients is also obtained.  Antiplatelet and statins remain the mainstay of medical management of stroke.

A notable potential complication after fibrinolytic therapy is hemorrhagic transformation. Hemorrhagic transformation is classified as hemorrhagic infarction and parenchymal hematoma, each with 2 subsets. Predictive factors for the occurrence of this complication include increased infarction area, gray matter location, atrial fibrillation, and cerebral embolism, acute hyperglycemia, low platelet count, and poor collateral circulation. [13]

When to start anticoagulation in patients with atrial fibrillation after acute stroke is always a dilemma. Usually, it depends on various factors like the size of the stroke and other comorbidities. Usually, if the size of the stroke is smaller to moderate and no hemorrhage, we start anticoagulation in 7-14 days. [14]

Some times there are patients with small hemorrhagic transformation after acute stroke, and in this scenario, it is better to wait for anticoagulation for a couple of weeks. This delay is not associated with excessive stroke recurrence. [15]

For patients with significant disabilities, physical therapy and occupational therapy consults should be obtained.  Similarly, if swallowing and speech are of concern, then speech/swallow consults should be obtained.  All patients should have follow-ups arranged with their primary care providers, and with neurology at appropriate times post-discharge. For symptomatic and significant carotid artery stenosis, referrals to vascular or neurological surgery should be sought.

The patient’s comorbidity has to be addressed and one should avoid hyperthermia. Oxygen supplementation is recommended when the oxygen saturation is less than 94%. Both hypo and hyperglycemia need to be addressed as they can affect the outcome.

Significant cerebral edema can occur after stroke and thus a CT scan should be done in patients who have altered mentation. Mannitol can be used but there is no evidence to support the routine use of corticosteroids. Patient position, hyperosmolar therapy, hyperventilation, and barbiturate coma may be used to lower the intracranial edema.

Seizures occur in about 15% of patients within the first few days of the stroke. Those who develop chronic seizures need treatment.

it is important to understand that palliative care is also an important component of stroke management. Some patients have a severe stroke and are incapacitated. Thus, one has to discuss end of life, palliation and do not resuscitation issues with the family.


Source:
MIT
Media Contacts: 
Abby Abazorius – MIT
Image Source:
The image is credited to the researchers/MIT.

Original Research: Open access
“Ferromagnetic soft continuum robots”. Yoonho Kim, German A. Parada, Shengduo Liu and Xuanhe Zhao.
Science Robotics. doi:10.1126/scirobotics.aax7329

LEAVE A REPLY

Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.